Holly Kramer, MD, is a nephrologist at Loyola University Medical Center and the editor in chief of 

Holly Kramer, MD

Crisis Point: The Cause and Calamity, Neighborhood Disadvantage and Kidney Disease

Clinicians often think of healthcare as having a problem and a solution, but what if there was more going on underneath the surface?

When it comes to the rising threat of developing 

, there's more at stake than the values we can measure in a lab. This Crisis Point focuses on the detrimental problem of neighborhood disadvantage as the cause and the calamity of kidney disease.

Neighborhood disadvantage is a place-based measure, defined as 1/5th of a population living below the federal poverty line, and with indices such as the Area Deprivation Index (ADI). Measurable data from the US Census Bureau identified 24 million Americans living in disadvantaged neighborhoods, with a disproportionate amount of racial and ethnic families residing within these communities. For example, only 4.3% of white Americans live in a disadvantaged neighborhood compared to 20.9% of black Americans.

These inequities don’t just present through poverty, housing instability, educational opportunities, employment, and access to resources. Neighborhood disadvantage trickles down the line, impacting an individual’s health through daily exposure to unfavorable conditions, including processed food, air pollution, and dehydration. As a result, the pathways to exposure to kidney disease can be represented by acute kidney injury (AKI), with repeated episodes accelerating CKD progression, and they can also be chronic, causing slow debilitating decline over the years.

“I really think that it asks nephrologists and other care providers to treat an individual's social context as part of their care plan,” said Maya Clark Cutaia, PhD, RN, in an interview with 

“We all walk in every day with those things on our backs. You may not see it, but we walk in with our history, our culture, our trauma, you know, our joys, whatever. And if we can take those real-world contexts and apply them to what we want to do next. It'll inform how we treat a patient.”

Statistically, 18.8 to 40 million Americans live within food deserts, characterized by a reliance on gas stations and convenience stores, limited or no access to fresh fruits and vegetables, and poor transportation options and unsafe spaces for exercise.

Having limited access to nutrient-dense options can take a major toll on kidney health. Often, the most affordable and easy choices in disadvantaged neighborhoods are chips, fried food, and sodas, of which the additives and high-sugar levels can build in the kidneys and contribute to inflammation. This differentiates from nephrologists’ kidney-friendly diet recommendations, which are a plant-based protein diet focused on whole foods and vegetables, while taking into account the risk of muscle loss for patients on dialysis.

Previous research has linked food deserts and disadvantaged communities with an increased risk of obesity. In kidney disease, obesity has been seen as both a 

 of further injury and disease progression. Thus, individuals living in disadvantaged communities face environmental factors that minimize their health and exacerbate poor outcomes, adding further barriers to care, especially 

Structural barriers in disadvantaged neighborhoods, such as distance to transplant centers, transportation burdens, and lack of local primary care physicians reflect systemic flaws in the catering of the healthcare system towards advantaged communities.

A majority of patients in these communities either lack awareness or the time to receive routine wellness checks related to the often silent disease of CKD. By the time a patient presents with symptoms of kidney deterioration, they’re often passed the point of early stages and require more in-depth treatment, according to experts. The issue of access and resources will not ultimately resolve itself once a patient presents with symptoms that need treatment.

Patients experiencing CKD in the later stages, especially end stage kidney failure (ESKD) will require dialysis, or in severe cases, transplantation. However, the barriers to care that existed in the beginning stages of their illness become even more pronounced once they require help.

“Neighborhood disadvantage puts people out of the running,” said Clark-Cutaia about the entire continuum of kidney care.

According to a recent study, neighborhood disadvantage is linked to a significant lack of access to waitlisting and kidney transplantation, especially living donor kidney transplantation. This reality can be seen as a representation of the double-sided nature of neighborhood disadvantage and kidney health as the root of the problem and a barrier to a solution.

To combat neighborhood disadvantage and its downstream effects, it is important to meet patients where they are. As clinicians, that means creating a presence in communities through churches, mosques, workplaces, farms, or by connecting with community leaders to build trust in the healthcare system.

Awareness and access can play a major role in improving patient outcomes. For example, on-site education and screening to reduce transportation/time burdens, along with mobile units for blood and urine testing can bypass systemic barriers and help patients get the preemptive help they need.

To address social determinants of health, clincians should aim to implement earlier screening and referrals and to connect patients to social workers for food transporation and social support needs.

Ethically and clinically, health care practitioners have a responsibility to their patients to treat neighborhood disadvantage as a clinical value and to find solutions for these barriers to care the same way they would treat an erroneous lab measure.

 is the inaugural Evelyn Lauder Associate Dean for Nurse Practitioner Programs and Professor at the Hunter-Bellevue School of Nursing at Hunter College.

 is a NIHR Advanced Fellow and Associate Professor (Principal Research Fellow) in Nutrition and Dietetics in the Centre of Obesity Research at University College London (UCL) and programme co-lead of the MSc Dietetics (Pre-registration) course at UCL.

 is the Chief Medical Officer at Evergreen Nephrology.

 is the Chief Executive Officer and Founder of Carna Health.

 is a nephrologist and Professor of Public Health Sciences and Medicine, Division of Nephrology and Hypertension at Loyola University Chicago, and the Editor in Chief of 

 is a postdoctoral researcher at the Leverhulme Centre for Demographic Science at the University of Oxford.

 is the Dr. Robert H and Eva M Moyad Research Professor of Urology, Co-Chief of Dow Division of Health Services Research, Professor of Internal Medicine, and Professor of Urology at the Medical School at the University of Michigan.

Editor’s Note: Cutaia declares no relevant disclosures. Brown reports no relevant disclosures. Pflederer reports relevant disclosures with Evergreen Nephrology. Viscomi reports relevant disclosures with Carna Health, Dama Health, QuantaBrain, and others. Shahinian reports no relevant disclosures.

Christie-Mizell CA. Neighborhood Disadvantage and Poor Health: The Consequences of Race, Gender, and Age among Young Adults. 

International Journal of Environmental Research and Public Health

Neighborhood Atlas - Home. Wisc.edu. Published 2018. 

https://www.neighborhoodatlas.medicine.wisc.edu/

Niculae A, Gherghina ME, Peride I, Tiglis M, Nechita AM, Checherita IA. Pathway from Acute Kidney Injury to Chronic Kidney Disease: Molecules Involved in Renal Fibrosis. 

International Journal of Molecular Sciences

Rhone A. USDA ERS - Documentation. Usda.gov. Published January 5, 2025. 

https://www.ers.usda.gov/data-products/food-access-research-atlas/documentation

American Kidney Fund. Kidney-friendly eating plan | American kidney fund. www.kidneyfund.org. Published December 1, 2021. 

https://www.kidneyfund.org/living-kidney-disease/healthy-eating-activity/kidney-friendly-eating-plan

Bellasi A, Di Lullo L, Di Iorio B. Chronic Kidney Disease: The Silent Epidemy. 

Li Y, Menon G, Kim B, et al. Residential Neighborhood Disadvantage and Access to Kidney Transplantation. 

https://doi.org/10.1001/jamanetworkopen.2025.49679

Videos

7 experts come together to address neighborhood disadvantage and its impact on kidney health in the latest Crisis Point. 

Just 1 year ago, semaglutide (Ozempic) was approved by the 

This approval marked an important milestone as the first GLP-1 receptor agonist to reduce the risk of worsening kidney disease, kidney failure, and death due to cardiovascular disease in these patient populations.

Semaglutide, initially developed by Novo Nordisk, received its first approval from the FDA under the name Ozempic on December 5, 2017. Its first indication was as an injection of 0.5 mg or 1 mg once weekly for glycemic control in patients with type 2 diabetes (T2D) – as an adjunct to diet and exercise.

Since then, semaglutide has exploded into nearly every related field. Glucagon-like peptide-1(GLP-1) receptors were discovered everywhere from the pancreas and the gastrointestinal tract to the heart, kidney, and liver. GLP-1 receptor agonists were quickly introduced into nephrology and cardiology, expanding their indications over the years to meet need in a variety of organs. Semaglutide has been at the forefront of this expansion due to its comparatively superior reductions of A1c, glucose, and overall weight.

In 2020, semaglutide received approval for the reduction of cardiovascular risk in patients with T2D, marking its entry into the cardiology sphere. In January of 2025, semaglutide became the first GLP-1 receptor agonist approved for worsening kidney disease, kidney failure, and death due to cardiovascular disease in patients with T2D and chronic kidney disease (CKD). This approval marked semaglutide’s entry into the full cardio-kidney-metabolic (CKM) disease spectrum, addressing mortality and worsening outcomes for major contributing diseases.

Now, just over a year after semaglutide’s approval for CKD, the editorial team at 

 has gathered insights from key clinicians across the CKM spectrum to discuss how this revolutionary drug overhauled the treatment landscape for kidney disease from all sides.

Semaglutide’s revolutionary impact on the endocrinology field cannot be understated. Despite not being the first, for years, this GLP-1 RA was the best method of reducing 3 major contributing factors to mortality in T2D. A1c reduction, glucose management, and weight loss saw substantial improvements as a result of the drug’s approval. However, semaglutide’s efficacy now extends far beyond T2D.

“I think that, sometimes, there’s hesitancy around starting a new therapy because the clinicians don’t know if other specialties will be on board,” Diana Isaacs, PharmD,

the director of Education and Training in Diabetes Technology and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and a member of 

 in an interview. “Now, we’re seeing through notes that nephrology is saying, ‘Why don’t you consider using semaglutide?’ And when they come to me as part of endocrinology, I see that, and I’m encouraged to use it. I think semaglutide really has enhanced team-based care in that we’re all on board.”

Isaacs went on to describe how semaglutide’s CKD approval provided a major paradigm shift for the American Diabetes Association’s standards of care.

“By showing its positive outcomes, particularly in people with kidney disease, semaglutide was paradigm-changing for the ADA Standards of Care and for our guidelines in that, previously, SGLT2 inhibitors were preferred for people with T2D and CKD,” Isaacs said. “Now, it’s either SGLT2 inhibitors or GLP-1 therapy – in practice, we’re now utilizing both of them.”

The Cardio-Kidney-Metabolic Landscape of Semaglutide

On October 9, 2023, the American Heart Association (AHA) released a presidential advisory regarding CKM syndrome, highlighting the interplay between metabolic risk factors, the cardiovascular system, and CKD. This syndrome has a significant impact on morbidity and mortality – poor CKM health, which is prominent among the American population, is associated with increased incidence of cardiovascular disease events.

“CKM syndrome encompasses the entire spectrum of risk, starting from people who have no risk factors or cardiovascular disease, going all the way through 

, vascular risk factors, subclinical disease, and clinical cardiovascular disease,” Janani Rangaswami, MD, professor of medicine at George Washington University and co-chair of the Scientific Advisory Group of the AHA’s presidential advisory on CKM Health, told 

 in an exclusive interview. “In any healthcare setting, the interplay between cardiology, nephrology, and endocrinology is the bulk of practice. In my practice, when I see individuals with kidney disease, diabetes alone is responsible for close to 50% of the cause of that kidney disease. When you add in obesity, metabolic dysfunction, and hypertension, all of these come together very heavily.”

Semaglutide’s approval for CKD effectively provided a bridge between all 3 specialties. When coupled with its initial diabetes indications and its cardioprotective effect, the drug was approved to tackle CKM syndrome on all fronts. Additionally, semaglutide’s efficacy when combined with SGLT2 inhibitors and RAAS blockade in patients with both CKD and high cardiovascular risk made it an effective tool for bolstering the protective effects of existing therapies. In this collaborative space between cardiology and nephrology, semaglutide became something of a miracle drug.

“While GLPs like semaglutide are very effective for A1c management and weight management, the FLOW trial really showed that this therapy saved lives, hearts, and kidneys,” Rangaswami said. “So now these therapies do multiple things; they’re addressing everything from improving lifespan to improving health outcomes, heart and kidney, and even beyond.”

The Bilateral Relationship Of CKD and Obesity

CKD remains one of the most common and serious complications of T2D, with obesity increasingly shaping disease trajectory, transplant eligibility, and therapeutic decision-making.

As global rates of obesity and CKD continue to climb, clinicians are paying closer attention to how excess adiposity directly affects renal physiology, independent of diabetes and hypertension.

“In obesity, metabolic demands increase, so the kidneys have to increase glomerular filtration rate and renal plasma flow to meet those demands. If nephron number is already reduced, the remaining nephrons have to work even harder. That leads to increased pressure inside each nephron, which causes barotrauma, scarring, and increased urine protein excretion,” explained Holly Kramer, MD, a nephrologist at Loyola University Medical Center and editor in chief of 

. “Severe obesity can also directly contribute to nephron loss through inflammatory effects. Often, obesity is accompanied by diabetes and hypertension, which further accelerate kidney disease progression.”

At BMI levels >40, systemic inflammation rises, adipokine signaling alters renal hemodynamics, and insulin resistance further increases glomerular stress. These processes frequently coexist with hypertension and T2D, amplifying cumulative kidney injury.

Despite this convergence of risk factors, CKD is often managed reactively rather than proactively. By the time patients reach end-stage kidney disease (ESKD) and require maintenance dialysis, obesity can create additional barriers to transplantation because of higher perioperative and postoperative complication risks. Increasingly, clinicians are focused on intervening earlier in the disease course.

In this landscape, GLP-1 agonists have emerged as a treatment strategy for patients with CKD and T2D, especially as a anti-imflammatory marker.

Subsequent research has shown an association of persistent low‑grade inflammation with worsened clinical outcomes in CKD, including faster eGFR decline, higher cardiovascular risk, and increased all‑cause mortality. Additionally, inflammation is a driving factor in the development and progression of T2D and its complications.

The reduction of inflammatory markers, such as CRP, has been highlighted as a potential clinical strategy to protect kidney function. In turn, semaglutide has been associated with reductions in CRP and other inflammatory markers independent of glycemic effects.

“GLP-1 receptor agonists have become another pillar we can use for people with chronic kidney disease. I see them being used as an adjunct to other medications, such as SGLT2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists. Especially when used in conjunction with those therapies, I think they have kidney benefits,” said Kramer. “They reduce urine albumin-to-creatinine ratios. If patients lose weight, we improve blood pressure control. If they have type 2 diabetes, glucose control improves. All of those factors help slow kidney disease progression, so I think GLP-1 receptor agonists are a great addition to our existing armamentarium.”

Where Obesity, CKD, and T2D Intersect with Semaglutide: The FLOW Trial

The approval for semaglutide for patients with T2D and CKD was based on data from FLOW, a phase 3b, multinational, parallel-group, double-blind, randomized, placebo-controlled trial investigating the effects of 1.0 mg once weekly semaglutide, a once-weekly GLP-1RA, on kidney outcomes in participants with CKD and T2D.

“I think it has largely removed the uncertainty that once existed around the effects of GLP-1 receptor agonists on kidney function and has clearly demonstrated that these agents are kidney-protective,” FLOW study investigator, Vlado Perkovic, MBBS, PhD, and provost at the University of New South Wales, told 

 “That, in turn, has informed guideline updates and helped the clinical community accept GLP-1 receptor agonists as a fourth pillar of care for people with diabetic kidney disease. That is a major advance.”

FLOW included 3533 participants with T2D and CKD, with the composite primary endpoint being time to first kidney failure, defined as persistent eGFR <15 ml/min/1.73 m2 or initiation of chronic kidney replacement therapy, persistent ≥50% reduction in eGFR, or death from kidney or cardiovascular causes.

Over a median follow-up of 3.4 years, semaglutide reduced the risk of a primary outcome event by 24% compared with placebo (331 vs 410 first events; HR, 0.76; 95% CI, 0.66-0.88; P = .0003). Similar reductions were observed for the kidney-specific composite (HR, 0.79; 95% CI, 0.66-0.94) and cardiovascular death (HR, 0.71; 95% CI, 0.56-0.89).

All confirmatory secondary outcomes favored semaglutide, including a slower annual decline in eGFR (difference, 1.16 mL/min/1.73 m²; P <.001), an 18% reduction in major cardiovascular events (HR, 0.82; 95% CI, 0.68-0.98; P = .029), and a 20% lower risk of all-cause mortality (HR, 0.80; 95% CI, 0.67-0.95; P = .01). Serious adverse events occurred in 49.6% of the semaglutide group versus 53.8% with placebo.

Beyond Weight Loss: Inflammation and Future Directions of Semaglutide

Perkovic emphasized that FLOW was not intended to be a weight-loss trial, with a broad range of BMIs among participants, including 25% with BMI <27. While GLP-1 receptor agonists, especially semaglutide and emerging combination therapies, present efficacy regarding weight loss, FLOW indicated semaglutide’s specific kidney benefits not simply attributable to obesity treatment.

However, Perkovic also remarked on patterns from the FLOW trial’s participant population, where the mean BMI was 32. Additionally, in the CREDENCE trial, which also evaluated patients with T2D and CKD, the mean BMI was 31. This highlights obesity as a prevalent, rather than incidental, comorbidity in contemporary CKD populations. Taken together, these findings underscore the importance of considering body weight as a core component of CKD risk assessment, rather than a secondary concern.

“What that tells us is that people with diabetes and kidney disease are, on average, significantly overweight and often fall into the obese category. Many of these patients are therefore likely to benefit from weight loss as well,” explained Perkovic. “These therapies address multiple, parallel pathologies that commonly coexist in our patients, which makes them particularly exciting. It also raises the question of whether more potent agents that induce greater weight loss might confer additional kidney benefits, something that still needs to be tested.”

As obesity, T2D, and CKD increasingly converge in clinical practice, therapies capable of targeting overlapping metabolic, hemodynamic, and inflammatory pathways may redefine standard care. For clinicians managing complex kidney disease populations, GLP-1 receptor agonists now represent not simply a metabolic adjunct, but a foundational component of comprehensive CKD risk reduction.

Isaacs reports disclosures with Dexcom, Abbott, Lilly, Novo Nordisk, Medtronic, Insulet, and others.

Rangaswami reports relevant disclosures with the Veterans Health Administration, Boehringer Ingelheim, Bayer, Procyrion, and the American Heart Association.

Kramer reports relevant disclosures with Bayer, Alexion, American Journal of Kidney Disease, National Kidney Foundation, and others.

Perkovic reports relevant disclosures with AstraZeneca, Bayer, Boehringer Ingelheim, and others.

Novo Nordisk. Novo Nordisk Receives FDA Approval of OZEMPIC (semaglutide) Injection For the Treatment of Adults with Type 2 Diabetes. 

. December 5, 2017. Accessed February 19, 2026. 

https://www.prnewswire.com/news-releases/novo-nordisk-receives-fda-approval-of-ozempic-semaglutide-injection-for-the-treatment-of-adults-with-type-2-diabetes-300567052.html

Knudsen LB, Lau J. The Discovery and Development of Liraglutide and Semaglutide. 

Novo Nordisk. FDA approves Ozempic for cardiovascular risk reduction in adults with type 2 diabetes and known heart disease, updates Rybelsus label. 

. January 16, 2020. Accessed February 19, 2026. 

https://www.prnewswire.com/news-releases/fda-approves-ozempic-for-cardiovascular-risk-reduction-in-adults-with-type-2-diabetes-and-known-heart-disease-updates-rybelsus-label-300988672.html

Anderer S. FDA approves semaglutide to reduce risk of kidney disease progression. 

Ndumele CE, Rangaswami J, Chow SL, et al. Cardiovascular-kidney-metabolic health: A presidential advisory from the American Heart Association. 

Furth SL, Colhoun HM, Kanbay M, et al. The relationship between obesity and chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. 

. Published online September 2025:S0085-2538(25)007744. doi:

https://doi.org/10.1016/j.kint.2025.09.019

Good PI, Li L, Hurst HA, et al. Low nephron endowment increases susceptibility to renal stress and chronic kidney disease. 

https://doi.org/10.1172/jci.insight.161316

Wang H, Fan K, Ning Y, et al. Hypertension and BMI as Mediators of Type 2 Diabetes-Induced CKD: Insights from an Integrative Multi-Database Study. 

Perkovic V. Inflammation Emerges as Promising CKD Treatment Target, With Vlado Perkovic, MBBS, PhD. HCPLive. Published February 9, 2026. Accessed February 20, 2026. 

https://www.hcplive.com/view/inflammation-emerges-as-promising-ckd-treatment-target

Rossing P, Baeres FMM, Bakris G, et al. The rationale, design and baseline data of FLOW, a kidney outcomes trial with once-weekly semaglutide in people with type 2 diabetes and chronic kidney disease. 

Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. 

Pruijm M, Belmar N, Bjornstad P, et al. REMODELing mechanistic trials for kidney disease: a multimodal, tissue-centered approach to understand the renal mechanism of action of semaglutide. 

https://doi.org/10.1016/j.kint.2025.10.005

Articles

Semaglutide has expanded from a T2D glycemic agent to a cardio-kidney-metabolic therapy, culminating in FDA approval for reducing CKD progression, kidney failure, and CV death in T2D with CKD. Cross-specialty adoption is accelerating, reshaping guideline positioning alongside SGLT2 inhibitors and enabling combination strategies with RAAS blockade and nsMRAs. Obesity is increasingly recognized as a direct mediator of renal injury via hyperfiltration, inflammation, and nephron stress, influencing progression and transplant candidacy. FLOW established kidney and survival benefits beyond weight loss.

1 year into real-world use, 4 clinicians discuss how semaglutide is transforming the endocrinology, nephrology, and cardiology landscape.


1 Year After CKD Approval, Semaglutide Transforms Diabetes, Kidney, and Heart Care

 continue to rise as global clinical challenges, the intersection between excess weight and kidney function has become increasingly important to patient outcomes and disease progression.

To discuss the association between excess adiposity, defined as a body mass index (BMI) ≥30 kg/m², and impaired renal function, HCPLive spoke with 2 experts in nephrology to glean insights relevant to clinical practice.

Each kidney contains a finite number of nephrons, ranging from approximately 200,000 to 2 million per kidney. As body mass increases, metabolic demand rises, prompting compensatory increases in glomerular capillary pressure, intraglomerular flow, and single-nephron glomerular filtration. Over time, this sustained hyperfiltration places mechanical stress on the glomerulus, contributing to podocyte injury, glomerulosclerosis, proteinuria, and progressive nephron loss. Obesity itself has been independently linked to these pathophysiological changes, even after accounting for common comorbidities such as diabetes and hypertension.

This physiologic strain becomes more pronounced at increased levels of adiposity, where 

obesity may contribute directly to renal injury

“Severe obesity, like a BMI above 40, can also lead to nephron loss itself because of the inflammatory effects obesity has on the body,” explained Holly Kramer, MD, a nephrologist at Loyola University Medical Center and editor in chief of 

The inflammatory burden associated with severe obesity may help explain why individuals with higher BMI often experience more rapid CKD progression, even in the absence of advanced disease at baseline.

Clinical trial populations have also highlighted the frequent coexistence of impaired kidney function and elevated BMI. Vlado Perkovic, MBBS, PhD, the provost at the University of New South Wales and an investigator in the FLOW trial, has observed this pattern firsthand.

FLOW, which evaluated kidney outcomes in adults with type 2 diabetes (T2D) and CKD, was not designed as a weight-loss study and did not include BMI-based eligibility criteria. Participants were enrolled based on kidney disease parameters, including an estimated glomerular filtration rate (eGFR) of 25–75 mL/min/1.73 m² and a urine albumin-to-creatinine ratio (UACR) of >300–<5000 mg/g, or 100–5000 mg/g among those with an eGFR of 25–<50 mL/min/1.73 m². Notably, a quarter of patients had a BMI <27 in the FLOW trial.

Despite this, the mean BMI of participants in the FLOW trial was 32. Similarly, the CREDENCE trial, which also did not focus on weight loss, reported an average BMI of 31. This highlights obesity as a prevalent, rather than incidental, comorbidity in contemporary CKD populations. Taken together, these findings underscore the importance of considering body weight as a core component of CKD risk assessment, rather than a secondary concern.

“What that tells us is that people with diabetes and kidney disease, on average, are very overweight,” said Perkovic. “And certainly are likely to benefit from weight loss as well. These are wonderful treatments that help address multiple sorts of parallel pathologies that are developing in many of our patients, and it's exciting to think about the future and whether some of the more potent agents that produce even more weight loss might.”

 Utilizing diet to prevent obesity, preserve kidney function, with Holly Kramer, MD. 

https://www.hcplive.com/view/utilizing-diet-prevent-obesity-preserve-kidney-function-holly-kramer-md

Podcasts

Obesity is common in CKD and drives hyperfiltration, nephron stress, and progressive kidney injury, according to experts, Kramer and Perkovic, and trial data. 


 Obesity’s Double Role in CKD as Comorbidity and Driver

Utilizing Diet to Prevent Obesity, Preserve Kidney Function, With Holly Kramer, MD

and the risk the comorbidity poses to renal function may alleviate the development of 

 before end-stage kidney disease (ESKD), according to an expert.

New insights from Holly Kramer, MD, a nephrologist at Loyola University Medical Center and editor in chief of 

, suggest clinical management, especially referring patients to dieticians early, can temper the pathophysiological mechanisms of obesity, which independently contribute to renal injury.

While obesity has been independently associated with CKD progression, certain individuals may be predisposed to the glomerular effects based on their nephron number from birth. Their nephron endowment can range from 200,000 to 2 million per kidney, and is determined by genetic and environmental factors during gestation. 

A reduced nephron endowment increases the risk for hypertension and CKD due to reduced renal functional capacity and compensatory glomerular hypertrophy. Other causes of reduced nephron count include premature birth, genetics, or conditions like diabetes or chemotherapy.

When an individual has obesity, the kidney’s response is to increase glomerular capillary pressure, intraglomerular flow, and filtration at the level of each nephron. When intraglomerular hypertension is sustained, it can lead to mechanical stress on the glomerular basement membrane, podocyte injury and loss, glomerulosclerosis, progressive nephron dropout, and proteinuria.

Once nephron depletion transpires, an individual's remaining nephrons become exposed to increased levels of hyperfiltration, reinforcing a feedback loop. This fuels the hyperfiltration hypothesis of CKD progression, with obesity revealing itself as a strong physiologic driver.

“So it's kind of like if you had a shoe factory and you fire, you know, three fourths of your employees, and then all of a sudden you say, Oh, by the way, we have to make three times as many shoes as what we normally do, you know,” explained Kramer, in an interview with 

“And so people get tired in that shoe factory. Same thing with those nephrons. In the setting of obesity and reduced nephron number, they just kind of wear out.”

At increased levels of body mass index (BMI), especially those > 40, systemic inflammation increases, adipokine signaling alters renal hemodynamics, and insulin resistance worsens glomerular stress. Additionally, patients often experience comorbidities of hypertension and diabetes, which can cause more damage to the kidneys.

Often, clinical management of these symptoms can be delayed until patients reach ESKD and are on maintenance dialysis. Once patients reach this stage, obesity can pose barriers to receiving a transplant because of increased risk for complications during and after surgery.

“Only about 10% of patients ever meet with a registered dietitian. But when they get on dialysis, everybody talks with the dietitian,” said Kramer. “It really makes sense that we should try to get our patients to be talking with a registered dietitian to slow kidney disease progression and get them to eat healthier.”

Kramer emphasizes the importance of medical nutrition therapy, which is covered by Medicare and most private insurances, and is crucial for managing kidney disease. She encourages patients to consult registered dietitians, either through telehealth or via the National Kidney Foundation's directory, to take disease management into their own hands, slow kidney disease and adopt healthier eating habits.

Kovesdy CP, Furth SL, Zoccali C. Obesity and Kidney Disease. 

Canadian Journal of Kidney Health and Disease

Villani G, Zaza P, Lamparelli R, Maffei G. Kidney volume-to-birth weight ratio as an estimate of nephron endowment in extremely low birth weight preterm infants. 

https://doi.org/10.1038/s41598-024-64897-6

Garske KM, Kar A, Comenho C, et al. Increased body mass index is linked to systemic inflammation through altered chromatin co-accessibility in human preadipocytes. 

https://doi.org/10.1038/s41467-023-39919-y

National Kidney Foundation. Nutrition and Kidney Disease, Stages 1-5 (Not on Dialysis). National Kidney Foundation. Published 2024. 

https://www.kidney.org/kidney-topics/nutrition-and-kidney-disease-stages-1-5-not-dialysis

Clinicians can provide dietitian intervention to reduce the risk of obesity, which is independently associated with CKD.  
